Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome
Abstract Background Acute chest syndrome (ACS) is the leading cause of mortality in sickle cell disease (SCD). The pathogenesis of ACS is complex and not entirely understood with multiple etiologies likely contributing simultaneously. One particular etiology is pulmonary vascular occlusion due to th...
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Pilot and Feasibility Studies |
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| Online Access: | http://link.springer.com/article/10.1186/s40814-020-00715-w |
| _version_ | 1818459474536431616 |
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| author | Craig D. Seaman Enrico Novelli Laura De Castro Margaret V. Ragni |
| author_facet | Craig D. Seaman Enrico Novelli Laura De Castro Margaret V. Ragni |
| author_sort | Craig D. Seaman |
| collection | DOAJ |
| description | Abstract Background Acute chest syndrome (ACS) is the leading cause of mortality in sickle cell disease (SCD). The pathogenesis of ACS is complex and not entirely understood with multiple etiologies likely contributing simultaneously. One particular etiology is pulmonary vascular occlusion due to thrombosis. Thus, anticoagulation is an attractive therapeutic modality. Methods This was a single-center, randomized controlled, open-label, pilot study to determine the feasibility of performing a larger multicenter phase III trial to assess the effects of unfractionated heparin (UFH) in ACS. Subjects were randomized within 24 h of diagnosis of ACS to one of two treatment arms, UFH, and standard of care (SOC), or no UFH and SOC. UFH was given intravenously for 7 days, or until discharge, if discharge was shorter than 7 days. SOC consisted of intravenous fluids, antibiotics, supplemental oxygen, analgesia, red blood cell transfusion, and exchange transfusion. Results From July 2014 to June 2018, a total of 7 patients underwent randomization (four patients received UFH in addition to SOC and 3 patients received SOC only). Two of the prespecified feasibility criteria were not met: the capacity to consent eligible individuals and the timely notification of hospitalized patients with ACS necessary to permit randomization within 24 h of diagnosis; thus, as a result of poor enrollment, the study was terminated early. The duration of hospitalization was 279.43 (SD 267.98) and 127.31 (SD 137.70) h in the UFH and SOC arms, respectively. The duration of hypoxemia, leukocytosis, fever, and moderate to severe pain was 117.52 (SD 60.52), 24.90 (SD 29.69), 117.52 (SD 60.52), and 117.52 (SD 60.52) h, respectively, in the UFH group, and 51.49 (SD 44.79), 0, 53.11 (SD 25.06), and 88.68 (SD 72.77) h, respectively, in the SOC group. No major bleeding was noted in either group. Conclusions Our study did not achieve prespecified feasibility criteria, resulting in poor enrollment and early termination, and serves to highlight some of the pitfalls experienced in clinical research in SCD. It did show the use of UFH without any major adverse events in 7 subjects. No future large-scale study is planned. Trials registration Registered at ClinicalTrials.gov (NCT #02098993) on March 28, 2014. |
| first_indexed | 2024-12-14T23:14:56Z |
| format | Article |
| id | doaj.art-61e99cf7b0074eb686a42759b3280bc0 |
| institution | Directory Open Access Journal |
| issn | 2055-5784 |
| language | English |
| last_indexed | 2024-12-14T23:14:56Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Pilot and Feasibility Studies |
| spelling | doaj.art-61e99cf7b0074eb686a42759b3280bc02022-12-21T22:44:06ZengBMCPilot and Feasibility Studies2055-57842020-11-01611810.1186/s40814-020-00715-wUnfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndromeCraig D. Seaman0Enrico Novelli1Laura De Castro2Margaret V. Ragni3Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical CenterDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical CenterDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical CenterDepartment of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical CenterAbstract Background Acute chest syndrome (ACS) is the leading cause of mortality in sickle cell disease (SCD). The pathogenesis of ACS is complex and not entirely understood with multiple etiologies likely contributing simultaneously. One particular etiology is pulmonary vascular occlusion due to thrombosis. Thus, anticoagulation is an attractive therapeutic modality. Methods This was a single-center, randomized controlled, open-label, pilot study to determine the feasibility of performing a larger multicenter phase III trial to assess the effects of unfractionated heparin (UFH) in ACS. Subjects were randomized within 24 h of diagnosis of ACS to one of two treatment arms, UFH, and standard of care (SOC), or no UFH and SOC. UFH was given intravenously for 7 days, or until discharge, if discharge was shorter than 7 days. SOC consisted of intravenous fluids, antibiotics, supplemental oxygen, analgesia, red blood cell transfusion, and exchange transfusion. Results From July 2014 to June 2018, a total of 7 patients underwent randomization (four patients received UFH in addition to SOC and 3 patients received SOC only). Two of the prespecified feasibility criteria were not met: the capacity to consent eligible individuals and the timely notification of hospitalized patients with ACS necessary to permit randomization within 24 h of diagnosis; thus, as a result of poor enrollment, the study was terminated early. The duration of hospitalization was 279.43 (SD 267.98) and 127.31 (SD 137.70) h in the UFH and SOC arms, respectively. The duration of hypoxemia, leukocytosis, fever, and moderate to severe pain was 117.52 (SD 60.52), 24.90 (SD 29.69), 117.52 (SD 60.52), and 117.52 (SD 60.52) h, respectively, in the UFH group, and 51.49 (SD 44.79), 0, 53.11 (SD 25.06), and 88.68 (SD 72.77) h, respectively, in the SOC group. No major bleeding was noted in either group. Conclusions Our study did not achieve prespecified feasibility criteria, resulting in poor enrollment and early termination, and serves to highlight some of the pitfalls experienced in clinical research in SCD. It did show the use of UFH without any major adverse events in 7 subjects. No future large-scale study is planned. Trials registration Registered at ClinicalTrials.gov (NCT #02098993) on March 28, 2014.http://link.springer.com/article/10.1186/s40814-020-00715-wAcute chest syndromeHeparinSickle cell diseaseThrombosis |
| spellingShingle | Craig D. Seaman Enrico Novelli Laura De Castro Margaret V. Ragni Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome Pilot and Feasibility Studies Acute chest syndrome Heparin Sickle cell disease Thrombosis |
| title | Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome |
| title_full | Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome |
| title_fullStr | Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome |
| title_full_unstemmed | Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome |
| title_short | Unfractionated heparin in acute chest syndrome: a pilot feasibility randomized controlled trial of unfractionated heparin vs. standard of care in acute chest syndrome |
| title_sort | unfractionated heparin in acute chest syndrome a pilot feasibility randomized controlled trial of unfractionated heparin vs standard of care in acute chest syndrome |
| topic | Acute chest syndrome Heparin Sickle cell disease Thrombosis |
| url | http://link.springer.com/article/10.1186/s40814-020-00715-w |
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